This project will study synthesis of compounds which are structurally related to tetrodotoxin that are neuro-blocking agents. Such compounds act by selectively blocking the transient sodium transport across membranes of activated nerve axons. Previous studies have shown that modification of the tetrodotoxin structure at positions six or eleven, remote from the guanidine moiety, retain the activity of tetrodotoxin. These findings will be extended by studying practical ways of synthesizing analogs which will allow the incorporation of radioactive tritium and carbon into the colecule and will also allow making active fluorescent, photoaffinity, and spin labeled analogs of tetrodotoxin. Such compounds will be valuable in neuro-physiological research and hold out the possibility of developing a practical local anesthetic base on the unique sodium channel blocking action of TTX.